CampylobaCter jejuni INDUCES EXTRA-INTESTINAL IMMUNE RESPONSES VIA TOLL-LIKE-RECEPTOR-4 SIGNALING IN CONVENTIONAL IL-10 DEFICIENT MICE WITH CHRONIC COLITIS

Campylobacter jejuni is one of the predominant causes for foodborne bacterial infections worldwide. We investigated whether signaling of C. jejuni-lipoproteins and -lipooligosaccharide via Toll-like-receptor (TLR) -2 and -4, respectively, is inducing intestinal and extra-intestinal immune responses following infection of conventional IL-10−/− mice with chronic colitis. At day 3 following oral infection, IL-10−/− mice lacking TLR-2 or TLR-4 harbored comparable C. jejuni strain ATCC 43431 loads in their colon. Interestingly, infected TLR-4−/− IL-10−/− mice displayed less compromized epithelial barrier function as indicated by lower translocation rates of live gut commensals into mesenteric lymphnodes (MLNs), and exhibited less distinct B lymphocyte responses in their colonic mucosa as compared to naїve IL-10−/− controls. Furthermore, in extra-intestinal compartments such as MLNs and spleens, abundance of myeloid cells was less distinct whereas relative percentages of activated T helper cells and cytotoxic T cells were higher in spleens and dendritic cells more abundant in MLNs of infected IL-10−/− animals lacking TLR-4 as compared to IL-10−/− controls. Taken together, in conventionally colonized IL-10−/− mice, TLR-4, but not TLR-2, is involved in mediating extra-intestinal pro-inflammatory immune responses following C. jejuni infection. Thus, conventional IL-10−/− mice are well suited to further dissect mechanisms underlying Campylobacter infections in vivo.